liu.seSearch for publications in DiVA
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
HSV-2 Cellular Programming Enables Productive HIV Infection in Dendritic Cells
Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. North Carolina State Univ, NC USA.
Linköping University, Department of Clinical and Experimental Medicine, Division of Hematopoiesis and Developmental Biology. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Hematopoiesis and Developmental Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical genetics.
Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. King Khalid Univ, Saudi Arabia.
Show others and affiliations
2019 (English)In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 10, article id 2889Article in journal (Refereed) Published
Abstract [en]

Genital herpes is a common sexually transmitted infection caused by herpes simplex virus type 2 (HSV-2). Genital herpes significantly enhances the acquisition and transmission of HIV-1 by creating a microenvironment that supports HIV infection in the host. Dendritic cells (DCs) represent one of the first innate cell types that encounter HIV-1 and HSV-2 in the genital mucosa. HSV-2 infection has been shown to modulate DCs, rendering them more receptive to HIV infection. Here, we investigated the potential mechanisms underlying HSV-2-mediated augmentation of HIV-1 infection. We demonstrated that the presence of HSV-2 enhanced productive HIV-1 infection of DCs and boosted inflammatory and antiviral responses. The HSV-2 augmented HIV-1 infection required intact HSV-2 DNA, but not active HSV-2 DNA replication. Furthermore, the augmented HIV infection of DCs involved the cGAS-STING pathway. Interestingly, we could not see any involvement of TLR2 or TLR3 nor suppression of infection by IFN-beta production. The conditioning by HSV-2 in dual exposed DCs decreased protein expression of IFI16, cGAS, STING, and TBK1, which is associated with signaling through the STING pathway. Dual exposure to HSV-2 and HIV-1 gave decreased levels of several HIV-1 restriction factors, especially SAMHD1, TREX1, and APOBEC3G. Activation of the STING pathway in DCs by exposure to both HSV-2 and HIV-1 most likely led to the proteolytic degradation of the HIV-1 restriction factors SAMHD1, TREX1, and APOBEC3G, which should release their normal restriction of HIV infection in DCs. This released their normal restriction of HIV infection in DCs. We showed that HSV-2 reprogramming of cellular signaling pathways and protein expression levels in the DCs provided a setting where HIV-1 can establish a higher productive infection in the DCs. In conclusion, HSV-2 reprogramming opens up DCs for HIV-1 infection and creates a microenvironment favoring HIV-1 transmission.

Place, publisher, year, edition, pages
FRONTIERS MEDIA SA , 2019. Vol. 10, article id 2889
Keywords [en]
HSV-2; HIV-1; HSV-2 and HIV-1 coinfection; dendritic cells; immune responses; DNA sensors
National Category
Microbiology in the medical area
Identifiers
URN: urn:nbn:se:liu:diva-163036DOI: 10.3389/fimmu.2019.02889ISI: 000504085400001PubMedID: 31867020OAI: oai:DiVA.org:liu-163036DiVA, id: diva2:1384256
Note

Funding Agencies|Swedish Research CouncilSwedish Research Council [AI52731]; Swedish Physicians against AIDS Research Foundation; Swedish International Development Cooperation Agency; SIDA SARC; VINNMER for VinnovaVinnova; Linkoping University Hospital Research Fund; CALF; Swedish Society of Medicine; Medical Research Council of Southeast Sweden

Available from: 2020-01-09 Created: 2020-01-09 Last updated: 2020-04-28

Open Access in DiVA

fulltext(4311 kB)30 downloads
File information
File name FULLTEXT01.pdfFile size 4311 kBChecksum SHA-512
d877fe6005aa414c0dfaaf91f55740cb64d645eb5929d77b2b0eeef767e36a28a38ab830a062e1ab36d73f073c4bcde8e6ce8afbecbc1333dc667a50faab11a6
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Crisci, ElisaSvanberg, CeciliaEllegård, RadaKhalid, MohammadHellblom, JuliaOkuyama, KazukiBhattacharya, PradyotNyström, SofiaLarsson, Marie
By organisation
Division of Microbiology and Molecular MedicineFaculty of Medicine and Health SciencesDivision of Hematopoiesis and Developmental BiologyClinical geneticsDepartment of Clinical Immunology and Transfusion Medicine
In the same journal
Frontiers in Immunology
Microbiology in the medical area

Search outside of DiVA

GoogleGoogle Scholar
Total: 30 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 49 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf